The Daily Transcript

Daily news and views from a postdoctoral fellow in Cell Biology.UCACACCUGGUGGAAGCUCUCUACCUAGUGUGCGGGGAACGAGGCUUCUUCUACACACCCAAGACCCGCCGGGAGGCAGAGGACCUGCAGGUGGGGCAGGUGGAGCUGGGCGGGGGCCCUGGUGCAGGCAGCCUGCAGCC

Friday, September 30, 2005

The Worst Things About Science

Had a conversation with Stefan about papers and dealing with reviewers (people that peer review your work and thus allowing it to be published). We got onto the topic of "Things we hate about Science". Well here goes:

1 - Being scooped. There is nothing worse than working your ass off for 4 years (much of it in the coldroom) when bang a paper comes out making all your work useless.

2 - Begging for money. When scientists are not working, eating, sleeping or at some seminar/conference, they are ... writing grants, fellowships ... aka begging. Their applications can be summarized as follows "I'm so great, my work is so important, look at how sexy my results are" but in reality they meant to say "if you don't give me this grant, my lab is going to sink into a deep black hole and my career is over!"

3 - Having a family. Being a scientist basically means being a workaholic. Why? Partially it's out of wanting to get things done, but mostly it's because of pressure ... "I need to get this last experiment done for my labmeeting/grant/paper/meeting with the supervisor" ... and if you think that scientists take the weekends off, think again. Most scientists I know work at least one day out of every weekend. In the end this workschedule (for some >50 hour workweek) leads to little time for unimportant things such as watching TV, and important things such as having a family. This is worse if you happen to be female, "pregnancy? I need to get my paper out!". This is a great frustration - and coupled to the fact that many institutions (such as my own) view scientific labor as cheap and plentiful, there is no economic incentive for the situation to improve - although it has been getting better as of late. The NIH's salary guidelines, to which most postdoc salaries are pegged, significantly increased a couple of years ago, but more can be done. For more on this topic click here.

4 - The pyramid scheme. Why do we tolerate the low pay, the long hours, the pain? (OK it's not that bad.) The reply goes like this "Dear student/postdoc/underling, one day you'll be a great PI (principal investigator, i.e. professor) and all your hard work will have paid off. I went through this, we all have to go through this stage, so now it's your turn to go through hell." All I have to say is ... Ponzi scheme.

5 - Reviewers. OK after a year(s) of work you compile enough data and a fancy model for a story/paper/article/publication. You send it in to a reasonable journal and they send it out for review. That's when the complicated song and dance of peer review starts. Some reviewers like it, some don't, some are reasonable, and some ARE OUT OF THEIR MIND. "That is a nice piece of work, but instead of just the moon, the authors should also get to Mars, Jupiter and alpha-Centauri before a) they can reasonably prove their assertions b) the manuscript can be acceptable for publication c) my bigshot buddy can publish his work and d) hasn't this been publish previously?" The editor (i.e. God) then has to officiate this poker match. Their rule of thumb can be summed up as "don't flinch". The moment that the editor sides with the manuscript's authors, the paper gets published ... and so their power rests in maintaining the status quo. The worst outcome of this exercise is that if the manuscript gets rejected, you then submit it to another journal AND HAVE TO GO THROUGH THIS TORTURE ALL OVER AGAIN. By the end of the protracted process (almost as long and painful as giving birth, I'm told) the paper gets published and you've survived a nervous breakdown and many sleepless nights ... only so others can FORGET TO CITE YOUR WORK WHEN THEY PUBLISH.

6 - Getting reagents from other labs. Ahhh the other song and dance. "Dear so and so, I really loved your paper (barely read it), interesting results (well actually they're pretty mediocre), we would like to test this idea (if I don't get this last piece of data that lousy reviewer #3 asked for, I'm screwed), could you send us a small amount (but not too small) of antibody/DNA/protein ... I promise to share any interesting results I get with you." Then if you're lucky they write back telling you "I need X, Y and Z's permission"/"I'm working on this same topic (i.e. get lost)". After a month and several emails (if you're very lucky) a poorly marked tube is sent to you. You use it only to find out that they sent the wrong thing. You inform them. They tell you that their staff changed and they can't locate the reagent. Then one day it finally arrives, it's what you asked for - great! You perform the experiment and ... a negative result.

7 - Tenure and other milestones. The most bizarre event I've ever seen is the "tenure process". It's a time of great stress, where Gandhi like figures turn into little Attilas. Magically your boss who use to be on your side is on your back. "Why weren't you here in the lab last Sunday night?" People flee the sinking ship, your boss looses 10lbs and half of his/her hair. Then it's over, your boss survived or he/she's moving to the University of North Dakota.

Then there are the other big milestones, the PhD thesis (i.e. procrastinate ... procrastinate ... furious writing ... 84 hours straight of writing), getting a professorship job (more begging ... and who know's where you'll end up). Each involves a distinct set of painful tasks which leads to many sleepless nights. Ahh, what fun it is to be in academic science!

OK I'll stop here for now ... but I'll continue this list some other time. If you have some other pet peeves about scientific research, let me know.

Thursday, September 29, 2005

Poster Time

Well time has come again to prepare for a meeting. This time it's the Jane Coffin Fellows - my funding agency. For some reason I could only find last year's newsletter online - but to get an idea of what this organisation is all about, click here.

This should be very interesting, many important Cell Biologists, Biochemists and Structural Biologists will be there. And I have to make a poster summarizing my postdoctoral career (today's task). The last meeting I attended was very successful - I met many individuals (all in my new adopted field) and learned a lot. In addition I was able to trek around the Canadian Rockies. This meeting is more general (in fact there is only one RNA person at the meeting and he does structural stuff), so this meeting's goal is to get exposed and be exposed. Should be fun.

Open Letter to the Discovery Institute

Alan I. Leshner ("Redefining Science" July 8) says intelligent design isn't science because scientific theories "explain what can be observed" and are "testable by repeatable observations and experimentation." But particular design arguments meet this standard. Biologist Michael Behe, for instance, argues that design is detectable in the bacterial flagellum because the tiny motor needs all its parts to function "is irreducibly complex" a hallmark of designed systems. The argument rests on what we know about designed systems, and from our growing knowledge of the cellular world and its many mechanisms.

How to test and discredit Behe's argument? Provide a continuouslyfunctional evolutionary pathway from simple ancestor to present motor.

Testing ID??? Ha! You guys don't even know what testing means! Testing means to attempt to falsify an idea.

DI guys, you need read some Popper. Here you are proposing to test EVOLUTION. You see evolution would make a prediction that you can test (i.e. "a continuously functional evolutionary pathway from simple ancestor to present motor"). If it fails the test then you've proved that evolution as we know it must be changed or discarded, it says nothing about ID. Furthermore ID makes NO PREDICTION. Think of it, you may test this motor, or how all the parts fit together, or WHATEVER ... and then any result you get you can conclude that THE DESIGNER(OR CREATOR) MADE IT SO. That is why ID is untestable, ID can never force a prediction, it can't be falsified. That is the flaw in you're half-baked arguement.

My oh my. These DI ... ID people. I think you need some real help. I could do a better job advocating for ID than you guys. So next time, before you make a fool of yourselves, run your "open letters" by me, I'LL VOLUNTEER TO PEER REVIEW YOUR CRAZY IDEAS.

We associate truth with convenience, with what most closely accords with self-interest and personal well-being or promises best to avoid awkward effort or unwelcome dislocation of life. We also find highly acceptable what contributes most to self-esteem.

This type of reasoning leads people to believe the strangest things (WMDs, "all government is bad government", ID ...). And that exactly sums up the problem with the discussion of issues in the American public sphere. And it gets me MAD.

Just because something is convenient, it doesn't make it true. This is exactly what a good scientist should be guarding against ... and I'll reiterate it again ... do not take anything for granted. You should be very careful in how you analyze data, because often we see what we want to see and miss the bigger picture. But I guess in some degree we are all trapped in our current paradigms.

I pulled out a postcard and subscribed to it. After about six months, I received a letter asking for my subscription dues. Jan had warned me that it took Seed Magazine forever to send his bill and then even longer to get his first issue. I mailed my check and waited.

Then this past week, Chris Mooney was all over the place promoting his book The Republican War on Science. We even saw him give a reading at Porter Square Books two days ago (see yesterday's post) where he was introduced as a correspondent for Seed Magazine. Jenni joked to me that we should go up and ask him about our subscription.

So what did we find in yesterday's mail? Our first copy of Seed. . Unfortunately we went to a concert at the NEC and didn't have the time to read anything in it, but this issue does looks good.

Thursday, September 22, 2005

Republican War on Science

I won't go through a lengthy synopsis of the book. Anyone who's been reading the news (from credible sources) and spends some time in a science department knows most of what the book is about.

But a couple of points:

- Since the late 1970s when Bill Kristiol of the Weekly Standard stated that companies should fund like minded intelectuals, and as a result these think tanks and "institutes" started poping up. Now the latest criticism of these creations is that they never publish stuff in peer review journals ... to counter this, these pseudo-scientific institutes are trying hard to publish. They are also launching THEIR OWN JOURNALS. Big question, how do you answer that type of tactic? Submit crazy articles to these strange new publications?

- More scientists have to take a public stand. Sure the National Academy of Science has issued statements, but where are the University presidents and the leaders of industry??? They need to raiuse trheir voices and that's where we (lowly profs, postdocs and grad-students) can apply pressure. WRITE TO YOUR UNIVERSITY/INSTITUTE PREESIDENT AND URGE THEM TO TAKE A PUBLIC STAND.

Wednesday, September 21, 2005

Where to do Stem Cell Research?

I read a nice article in the Whitehead Instituite Magazine (Paradigm) about Stem Cell research in Europe. Here is a link to the Spring 2005 issue. If you think that the US is not very permissive when it comes to stem cell research, look at this map of Europe and where stem cell research is prohibited and where it is permited:

What's new is that many of these signals are not freely diffusing around but are "packaged" into vesicles (see picture)!

First off I did not know that bacteria even made or secreted vesicles, but apparently some do, and this has been described before. And now these vesicle contain packets of information? Wow, those bacteria are more sophisticated than I'd ever imagined.

Friday, September 16, 2005

Types of RNA

mRNA - this stands for messenger RNA, and these represent the products of the majority of genes ... however by some estimates make up as little as 10% of the RNA in a cell at any given time.

rRNA - for ribosomal RNA. This forms the structural component of the ribosome, the machine that translates mRNA into protein. Interestingly, all the catalytic sites in the ribosome are formed by the bases coming off RNA. Click here for more on catalytic RNA.

tRNA - for ... well these types of RNA form a "t" shape. Each of these RNAs can recognize 1-3 codons (the 3 nucleotide code present in DNA and RNA) on one end via it's anti-codon loop and is attached to an amino acid via it's other end. As the ribosome "translates" mRNA into protein, tRNAs enter the ribosome and match amino acids to the mRNA's successive codons.

snRNAs - for small nuclear RNAs. These are catalytic RNAs that perform mRNA splicing.

miRNA - for micro RNA. These small RNAs are used to destroy mRNAs with complementary sequences. This process is called RNAi (for RNA interference).

The Scientific community, a brutal place

Seems like an observatory in Granada, Spain may have obtained information over the internet (using a search engine) to find data that a second group of scientists have been collecting for quite a while. It's entirely possible that the first group was indeed tracking the object and just discovered that they had competitors.

One thing that the public does not fully appreciate about Science is that it is a brutal place to work in. There is massive competition and you are constantly defending your views (or models) this leads to a massive amount of introspection regarding your beliefs and a fair amount of stress. Reading the news papers and watching stupid debates such as the whole ID affair I'm just amazed. Clowns like Michael Behe, who parades around misquoting people and never backing up his assertions with data, would perish in a moment in the highly competitive landscape of Science (at the highest level). People are constantly judged ... not on their personality but on the quality of their data, and the ability to come up with novel concepts and the INSIGHT their models provide. If you don't believe me go to PubMed (THE search engine for biological abstracts) and type in the search Behe_MJ. What do you get? 37 Abstracts. Here are the first 10:

OK so since 1993 what has he done? The last time he published an experiment on the bench was 1997 ... in BBRC??? (A third rate journal, sorry to all those that have published there, but it's the truth). And before that, a paper on how Histones (which are used to package DNA) can TOLERATE mutations (so much for his irreducible complexity) - and is actually not very interesting. If anything he makes a big deal about how histones could potentials change faster than they actually do. Then some other minor papers (#9,10). The rest? OPINIONS in various journals (#1,3,4,5,8) and a computer model of how its hard to evolve (#2) - hmm I guess he's trying to be a Systems Biologist.

Now there is some "politics" in Science, but compared to other fields it's not that bad, and there are so many institutes and funding agencies that even people who have many enemies, but still produce interesting data and models (sorry that disqualifies you Behe), can make a living and be heard in the scientific discussion.

Reading Behe's website, he sites all this old data he published over 10 years ago (except for the BBRC publication). This lab is dead. And what has he found, how nucleosomes bing poly-pyrimidine tracks? My oh my. Excuse me for sounding like some snotty Ivy League researcher, but my PhD thesis provided more insight than this guy's work! And this fight that he leads of ID over evolution is so stupid. But meanwhile real battles over data like the one above, or over models, rage on in Science ... out of the public spotlight.

Processing body = place where mRNA is decayed but perhaps also stored. RNAi also seems to take place there.

Stress granule = place where mRNA is stored when the cell faces "stress conditions".

I've seen mRNA go into granules when it's injected into the cytoplasm - so although these bodies, granules ... or what ever you want to call them ... are relatively new discoveries (the paper above is only one in a long series of papers), these structures are readily visible.

Sunday, September 11, 2005

Boston Bookclub

Had another bookclub meeting last night. This bookclub is just an excuse to get together once a month to eat and drink. We're so lazy that we need two months to read the book (most of the procrastination involves getting the book) So we alternate between reading a book and watching a thematically related movie every other meeting. We're currently reading Disgrace by J. M. Coetzee. But in the meanwhile we decided to watch East is East (a movie to compliment the book we just read - The Satanic Verses).

Friday, September 09, 2005

What went wrong

In the first interview, Dr Yossi Sheffi, a professor of engineering systems at MIT discusses the differences between organizations that survive and fail during crises. The bottom line is the organization's culture. Rapid exchange of information and an awareness of the ongoing events helps a lot. Another key aspect is flexibility. Dr Sheffi points out that often the best decisions are made by people at the front lines.

And finally this incompetent fool was firedreassigned. I hope that the government will operate less like a country club and more professionally (full of WELL TRAINED EXPERTS). Again my expectations are low, but the Brown dismissal is a good start(I guess I was too optimistic).

Thursday, September 08, 2005

Chimp Genome: A glimpse into how evolution works

I've glossed over the article in last week's Nature of the Pan troglodytes (Chimpanzee) genome. By comparing our DNA sequence with that of a species that had a common ancestor a hand full of million years ago we can see how our genome has changed since the split. A good chunk of the paper describes all these DNA elements that have been jumping, replicating and dying slow deaths inside of our DNA. Our chromosomes are literally zoos!

I won't give you a summary ... go visit Pharyngula for the score card.

One interesting finding is that certain alleles (version of a gene) that are associated with disease are the only version found in Chimps! For example the version of the PPAR Gamma gene (a gene that encodes a receptor on the surface of cells ... I think?) that is associated with type 2 diabetes is the only version of the gene found in chimps. What probably happened is that as we split both humans and chimps had the diabetes version, with no diabetes. As other genes changed in humans, due to selection pressures, PPAR-Gamma's function was slightly impaired in the new environment and thus caused diabetes with a higher frequency. Mutant versions of PPRA-Gamma appeared and alleviated these problems. Now the old version of PPAR-Gamma is in the population and is in the course of being selected against (as individuals with the old allele are on average less healthy and have fewer surviving descendents). Evolution at work!

Tuesday, September 06, 2005

Good Government vs God

Over the weekend we were up in the New Hampshire wilderness at a B&B, but I still couldn't get too far away from the events down south. Up there I heard from one individual that all the problems with looting and the breakdown of civil society was caused by a "loss in faith", faith in God that is.

I am really tired of religion (or lack of religion) being used by right wing apologists to explain all the evils of society. The problem is the person from NH wasn't a right wing nut. Frank Rich said it best, this is a result of faith based propaganda used by the government to squash all debate. Unfortunately many average Americans are under the spell. The current republican leaders all want to sweep inconvenient facts under the carpet, and their war against science is a symptom of this - and it has to stop. And now even the most ardent supporters are now asking questions (see the clip now before Fox forces ifilms to pull it). Even David Brooks. I hope that we'll learn from this tragedy. Faith is not enough. Government does play an important role in society, and starving the Government of resources can lead to chaos in times of desperation. We must hold those in charge responsible - why is the President saying that Michael Brown, the head of FEMA, is doing "a heck of a job"?? As the New Orleans Times-Picayun states in it's open letter to the president - the guy should be FIRED.

Friday, September 02, 2005

New Orleans is Sinking

"My memory is muddy what's this river I'm inNew Orleans is sinking and I don't want to swim"-The Tragically Hip

Incredible how vulnerable we are to the great forces that lie out there. We're nothing but ants on a thin crust, floating on a big ball of lava. Throw in some water and atmosphere ... and presto Earth.

Seeing all this chaos, I wonder how the future will look like. When the poles melt and the ocean rises, how will New York, Boston, Mumbai, Tokyo, Shanghai and other low lying cities cope? In New Orleans, like Venice, the earth it's sitting on is itself sinking. And on top of that storms are getting worse.

Insured damage from storms is rising for four reasons. One, more property is covered by insurance today than in the past. Two, the value of the property (as measured in dollars) has increased. Three, there is more building in coastal regions, on river floodplains, and in other high-risk areas. And four, storms are both more frequent and more powerful.

And as the oil prices rise, it's not just the cities, but the whole infrastructure of our economies that might just collapse.

Few countries have researched extensively the effect of rising seas on their economies and population distribution. A World Bank report concludes that a 1-meter sea level rise would inundate half of BangladeshÂs riceland. For a country with 133 million people projected to reach 209 million by 2050, the prospect of losing half of its rice harvest is not a pleasant one.

Thursday, September 01, 2005

Life and Water

In February I wrote a post on whether water was required for extra-terrestrial life, and whether NASA should be chasing water in it's search for aliens.

So what is needed for the generation of life de novo (from scratch)?

First we need a basic concept of what life is. For now lets just say that life is a self replicating entity. So the "search for life" could be substituted for "the search for self replicating entities". If life is going to start, it will most probably start with the simplest "entity", a molecule - most probably a polymer. Our quest then is "the search for self replicating polymers (and their descendants)" .

So what should we look for? Or what conditions are necessary for polymers to form?

Oxygen? Actually Oxygen would be a great impediment. Complicated molecules need to form large polymers. Oxygen, which likes to steal electrons from other molecules, would prevent the sharing of electrons (i.e. the covalent bonds) that are required for polymer formation. All geologic evidence points to the earth's original environment as being reducing (i.e. the opposite of oxidizing). Free oxygen first appeared on our planet after photosynthesis evolved. Are they asserting that photosynthesis (or a similar process) evolved on Mars? That is unlikely.

Do we need liquids of any sort? Since liquids are a good medium for chemical reactions, they would help, however polymers could also form in gaseous environments ...

So why are we searching for life on Mars? There is not much liquid. If there was any it was water. And the planet has an oxidative environment (as there is free oxygen and little evidence of reduced carbon). Besides mars is one big desert.

A more apt target would be a chemically rich planet with lots of activity ... like Venus.

I had initiated a vicious debate with some but now it seems that many are arriving at the same conclusion I had made (and I'm sure made by many others). So why do some insist that water is special? From an article in last week's edition of Nature on a conference on the subject held in Varenna, Italy:

Water has many properties that seem indispensable for the functioning of proteins and cells. It is an excellent solvent for ions, for example it's crucial for nerve signaling, enzymatic processes, biomineralization and the behavior of DNA. It is also a master of weak intermolecular interactions such as hydrogen bonds and hydrophobic forces. The latter play a central role in protein folding and protein−protein interactions, whereas the former often act as bridges between protein binding sites and their substrates. And water's ability to absorb and lose heat without undergoing a large temperature change provides thermal cushioning, shielding cells and organisms from wild temperature swings.

But then others such as Steven Brenner point out:

... water is generally not a good solvent for doing organic chemistry which is, in the end, what life is all about. For one thing, water is rather reactive, tending to split apart the bonds that link the building blocks of biomolecules together. It readily breaks peptide bonds, for example, as well as many of the bonds in nucleic acids, such as RNA. "The structure of RNA screams 'I did not arise in water!'" Benner asserts. He says that in about four out of five cases, synthetic organic chemists will avoid using water as a solvent.

Having said that the article reports:

"I think it is perfectly possible that at least elements of relevant biochemistry can be persuaded to work in a completely non-aqueous environment," says physicist John Finney at University College London. Finney points to evidence that enzymes can work in 'dry' air, where they hold on to only the barest coatings of water molecules, and even in non-aqueous solvents.

What are possible candidates?

Liquid Ammonia

Formamide

Liquid Hydrogen

Liquid Nitrogen

Liquid Methane

So what conclusions did the conference attendees make?

[T]he participants in Varenna generally agreed that life on Earth is adapted to water rather than the other way round. "Life on Earth itself is fine-tuned to water a consequence of it evolving in close association with the medium," says Finney. "To put it the other way is perhaps to put the cart before the horse."